近日，国际著名杂志Nature最新一期刊登了国外研究人员的最新研究成果“Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour。”，文章中，作者表示可卡因效应是可逆转的。
突触弹性已知会在药物上瘾中出现，但几乎没有证据将由药物激发的弹性与在药物上瘾的动物中所看到的行为适应性联系起来。Pascoli等人报告，表达I-型多巴胺受体的“多巴胺能神经元”中的特定“增强作用”（potentiation），会引起经常是在暴露于可卡因的动物中所观察到的运动敏感性增强效应。利用光遗传学手段对这一通道实施的特定“去增强作用”（depotentiation），既会恢复正常突触传输，又会消除行为表现型。这些数据将“表达D1R的神经元”的突触“增强作用”与由药物激发的行为联系了起来，并且说明，由可卡因诱导的适应性突触变化的治疗性逆转可能会导致行为纠正。（生物谷Bioon.com）
doi:10.1038/nature10709
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Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour
Vincent Pascoli, Marc Turiault & Christian Lüscher
Drug-evoked synaptic plasticity is observed at many synapses and may underlie behavioural adaptations in addiction1. Mechanistic investigations start with the identification of the molecular drug targets. Cocaine, for example, exerts its reinforcing2 and early neuroadaptive effects3 by inhibiting the dopamine transporter, thus causing a strong increase in mesolimbic dopamine. Among the many signalling pathways subsequently engaged, phosphorylation of the extracellular signal-regulated kinase (ERK) in the nucleus accumbens4 is of particular interest because it has been implicated in NMDA-receptor and type 1 dopamine (D1)-receptor-dependent synaptic potentiation5 as well as in several behavioural adaptations6, 7, 8. A causal link between drug-evoked plasticity at identified synapses and behavioural adaptations, however, is missing, and the benefits of restoring baseline transmission have yet to be demonstrated. Here we find that cocaine potentiates excitatory transmission in D1-receptor-expressing medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time course that parallels locomotor sensitization. Depotentiation of cortical nucleus accumbens inputs by optogenetic stimulation in vivo efficiently restored normal transmission and abolished cocaine-induced locomotor sensitization. These findings establish synaptic potentiation selectively in D1R-MSNs as a mechanism underlying a core component of addiction, probably by creating an imbalance between distinct populations of MSNs in the nucleus accumbens. Our data also provide proof of principle that reversal of cocaine-evoked synaptic plasticity can treat behavioural alterations caused by addictive drugs and may inspire novel therapeutic approaches involving deep brain stimulation or transcranial magnetic stimulation.
